Differences in the allosteric modulation by phenytoin of the binding properties of the sigma1 ligands [3H](+)-pentazocine and [3H]NE-100

The present study evaluated the effects of phenytoin (DPH) on the binding to synaptosomal fraction membranes from guinea pig brain of the prototypic sigma1 (sigma1) receptor agonist [3H](+)-pentazocine and the putative sigma1 antagonist [3H]NE-100. Equilibrium and binding kinetics studies were done....

Full description

Saved in:
Bibliographic Details
Published in:Synapse (New York, N.Y.) N.Y.), 2006-03, Vol.59 (3), p.152
Main Authors: Cobos, Enrique J, Lucena, Gema, Baeyens, José M, Del Pozo, Esperanza
Format: Article
Language:English
Subjects:
Analgesics, Opioid - metabolism
Animals
Anisoles - pharmacology
Anticonvulsants - metabolism
Anticonvulsants - pharmacology
Brain - drug effects
Brain - metabolism
Data Interpretation, Statistical
Guinea Pigs
In Vitro Techniques
Kinetics
Male
Membranes - metabolism
Pentazocine - metabolism
Phenytoin - metabolism
Phenytoin - pharmacology
Propylamines - pharmacology
Radioligand Assay
Receptors, Opioid, delta - drug effects
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The present study evaluated the effects of phenytoin (DPH) on the binding to synaptosomal fraction membranes from guinea pig brain of the prototypic sigma1 (sigma1) receptor agonist [3H](+)-pentazocine and the putative sigma1 antagonist [3H]NE-100. Equilibrium and binding kinetics studies were done. The order of affinity of 12 sigma1 ligands for binding sites labeled with [3H](+)-pentazocine correlated well with their order of affinity for sites labeled with [3H]NE-100, suggesting that both radioligands label the same receptor. Phenytoin increased the binding of [3H](+)-pentazocine, enhancing its affinity (K(D) value) for sigma1 receptors and decreasing its dissociation rate from these receptors. The maximal number of receptors (B(max) value) labeled with [3H](+)-pentazocine was not changed. In contrast, phenytoin decreased the specific binding and maximal number of receptors labeled with [3H]NE-100, and increased its dissociation rate from sigma1 receptors. The affinity of this radioligand for sigma1 receptors was not modified. In conclusion, phenytoin behaved as a positive allosteric modulator on the binding of [3H](+)-pentazocine, whereas it negatively modulated the binding of [3H]NE-100. These results add evidence in favor of the use of phenytoin in vitro to distinguish between agonists and antagonists of sigma1 receptors.
ISSN:0887-4476